# Genetic and environmental determinants of dental fluorosis: a case‒control study of DLX3, ESR1, and ESR2 variants in a high-fluoride region of Mexico

## TL;DR

This study explores how genetic factors and fluoride exposure influence the severity of dental fluorosis in women from a high-fluoride region in Mexico.

## Contribution

The study identifies specific gene variants (DLX3, ESR1) associated with mild and moderate dental fluorosis in a high-fluoride population.

## Key findings

- Higher fluoride in drinking water correlates with higher fluoride in urine.
- The rs2278163 DLX3 and rs12154178 ESR1 gene variants are linked to milder fluorosis severity.
- Fluoride in drinking water negatively correlates with mean corpuscular volume (MCV).

## Abstract

Dental fluorosis (DF) is a condition caused by prolonged fluoride (F) exposure during tooth development, leading to enamel changes. Clinically, it presents as opaque white spots and, in severe cases, striations, mottling, or enamel loss. Although chronic fluoride exposure is the main factor, severity does not always align with fluoride levels, suggesting genetic influences, such as variants in the DLX3, ESR1 and ESR2 genes, which regulate tooth development. This cross-sectional case–control study included 79 women from Durango, Mexico. The severity of dental fluorosis was assessed across the entire mouth via the Thylstrup–Fejerskov Index (TFI), with the highest score recorded for evaluation. The classification followed the World Health Organization (WHO) guidelines from Geneva, 1997, categorizing severity into mild, moderate, and severe groups. The fluoride concentrations in the water and urine were quantified via potentiometry. Genotyping was conducted via real-time PCR. The average concentration of fluoride (ppm) was 5.38(± 2.73 SD) for tap water, 4.79±(4.60 SD) for urine and 2.32(± 2.78 SD) for drinking water TFI followed the next distribution: 72.1% of the participants had moderate, 22.7% had mild, and 5.2% had severe fluorosis. A positive correlation between F in drinking water and F in urine. (0.46, p = 0.001) and a negative correlation between F in drinking water and the mean corpuscular volume (MCV) (-0.41, p = 0.01) was found. Additionally, a significant association was identified between the recessive model of the rs2278163 DLX3 and rs12154178 ESR1 polymorphisms and mild and moderate fluorosis (p = 0.02, OR = 0.25, 95% CI: 0.07–0.88 and p = 0.034, OR = 0.31, 95% CI: 0.10–0.95, respectively).